The aim of this research is to better define the interaction of acetylcholinesterase and nerve membranes. The possible orientation of this enzyme with respect to the membrane surface will be studied. In addition, changes in orientation and/or conformation upon chemical and electrical perturbation (stimulation) of the membrane will be investigated. Direct physical data relevant to the geometrical orientation of membrane associated proteins is sparse in general, and non-existent for acetylcholinesterase. The techniques of spin-labeling combined with EPR and fluorescence spectroscopy will be used. Spinlabel and fluorescent probes will be used to explore both the enzyme and the lipid contributions to the enzyme-membrane interaction. These studies will further our understanding of the molecular mechanism by which nerves function.